Vol. ll8, Novembe, Printed in
THE ,.JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
URIN CYTOLOGY: PATHOLOGIST'S PRECLINICAL CANCER? ·wILLIAM M. MURPHY From the Department of Pathology, Unioersity of Tennessee Center for the Health Sciences, Memphis, Tennessee
ABSTRACT
The reluctance to
as a diagnostic in urologic cancer has been of falsely results. The recent of the identification of urothelial the
LU,~.CLH.,v
Hl
carcinoma in situ and bladder was available for found
Case 2. A black woman onset of gross, painless hematuria 4 tion. An IVP revealed a filling defect Initially, the defect was confirmed on rP1rrn,arcirlP and blood was emanating from the left ureter at Washings from the left renal suspicious of low grade ously obtained urine Subsequently, hematuria studies returned to normal. The matic with negative x-rays and has not returned to the clinic. Case 3. A black man with with gross, painless contained cells bladder On review, the
""ot,,c:f'nn.v
Patients with positiue or suspicious urinary cytology Histologic Diagnoses MATERIAL AND METHODS
Transitional cell Ca lViixsd (transitional-squamous) cell Ca Primary Metastatic Carcinoma in situ Moderate/severe dysplasia
records confirmed carcinoma (see with bladder cancer for whom urihad been requested. Six other had to severe urothelial dysplasia. The sis had not been confirmed at the termination of 10 who are discussed in detail.
No. Pb. 2
6 5
10 2 6
agam considered suspicious (part c of figure). underwent transurethral resection of the patient was last seen 3 months hematuria was noted. Case 4. A black man was referred to our from a nearby custodial care hospital. The vvas unreliable but on examination the patient had gross hematuria a greatly distended bladder. tumor cells were found in 1 of 3 urine specimens d of Bladder biopsies revealed mild urothelial rhagic or denuded. At farcts were found. A diagnosis. The patient was rehospitalized 2 months later for upper gastrointestinal bleeding of unknown source, No quent evaluation has been done. Case 5. A 50-year-old black woman and flank pain. Roentgenograms revealed a
CASE REPORTS
--,··-,~m
Accepted for publication February 25, 1977. 8ll
812
MURPHY
Cells initially considered positive or suspicious for malignancy. On review original diagnoses were confirmed in all but were reinterpreted as mild atypic and reactive urothelium, respectively. Reduced from x 400.
calculus and a questionable filling defect at the left ureterovesical junction. Cystoscopy was done as well as left ureteral catheterization but no stone was discovered. Before the cystoscopy 2 urine specimens and 1 bladder washing were obtained, all of which were negative for malignancy. A urine specimen collected after ureteral instrumentation had papillary aggregates suspicious of neoplasm. No bladder biopsy was done. On cytologic review the suspicious cells were reinterpreted as mild urothelial atypia (part e of figure). The patient is currently being followed in the clinic. Case 6. A 24-year-old white woman was 26 weeks pregnant when hospitalized with gross hematuria and left flank pain. Cystoscopy and retrograde pyelography revealed a tortuous and dilated left ureter. After ureteral instrumentation 2 urine specimens were submitted for cytologic studies, 1 of which was considered positive. On review, it was apparent that the specimens contained reactive rather than neoplastic papillary aggregates (part f of figure). Case 7. A 46-year-old black woman had been followed at regular intervals for 5 years before hospitalization. At the initial evaluation the patient had a squamous papilloma of the bladder and, thereafter, had had numerous bladder biopsies and fulgurations for squamous metaplasia. Recently, 1
e
and f, which
bladder washing contained cells suspicious of a low grade neoplasm. Two previous specimens and 2 subsequent samples have been negative. The original diagnosis was confirmed on cytologic review (part g of figure). The patient continues to have biopsy-proved squamous metaplasia. Case 8. A 72-year-old black man had had multiple episodes of gross, painless hematuria for 3 years before hospitalization. Two bladder biopsies had revealed denuded urothelium and chronic inflammation of the lamina propria. Multiple small diverticula had been identified in a cystogram. Of 5 urine specimens 1 contained malignant tumor cells (part h of figure). At cystoscopy a biopsy of a friable urothelial lesion yielded tissue with acute and organizing inflammation but denuded epithelium. Urine specimens 3 months later were negative for malignancy. A deep bladder biopsy at that time revealed interstitial inflammation consistent with eosinophilic cystitis. On review the original cytology specimen again was interpreted as positive. The patient is currently being followed by his physician in another state. Case 9. An 87-year-old black man had had biopsy-proved, incompletely resected adenocarcinoma of the prostate gland for 9 years at the time of hospitalization. Cytologic evaluation of a single urine specimen revealed cells suspicious of malig-
FALSELY POSITIVE URINARY CYTOLOGY
died before other studies for necropsy was denied. Case 10. An extensive search failed to uncover this records, uu.o,H.vu
DISCUSSION
studied 10 had not had histologic confirmation or susp1c1ous report. A review of clinical ..,a,,uvn,"''" material was possible in 9 cases. The original was confirmed in 7 and all of these abnormalities. remaining patients were and reactive cwc:uui,,, respectively. Both µo.cn,rn,o had had ureteral instrumentation before the "'1-''"·'rn,cu was collected. Reactive and even normal urothelial from the upper collecting are difficult to evalularge cells that tend to ate. :2 , 13 These areas are lined groups. may have mimic a low grade neoplasm of data (not provided in these cases) specimen misinterpretations of this kind can be avoided. Of the 7 cases with unconfirmed or suspicious and available records 2 had transient of the caliceal systems. In 1 blood was emanatthe corresponding ureteral orifice at cystoscopy. The abnormal cells occurred in 0pv~cm,,~
!JU!-'ULV>HU
The data also reflect the limitations of urinary ""toloau Cells from the upper collecting system may resemble low grade bladder cancer and, until cytologic criteria can be better defined, specimens from the ureters and/or renal should be noted. Any disease or procedure that such cells to appear in the urine should be rP,rrnrm,n positive or suspicious specimen, unsupported cli.nicaI findings, should not occasion extensive diagnostic and/or therapeutic procedures but neither should it be ignored. Positive or suspicious urinary cytology in the presence of bladder outlet obstruction and/or persistent, albeit apparently uroth·· elial abnormalities, such as squamous metaplasia, or extensive urothelial denudation, requires careful surveiJ. lance. REFERENCES
l.. Foot, N. C., Papanicolaou, G. N., Holmquist, N. D. and J. F.: Exfoliative cytology of urinary sediments. A 2,829 cases. Cancer, 11: 127, 1958. 2. Esposti, P. L., Moberger, G. and Zajicek, J.: The diagnosis of transitional cell tumors of the and its histologic basis. A study of 567 cases of disorder including 170 untreated and 182 irradiated tumors. Acta Cytol., 14: 145, 1970. 3. de Voogt, H. J. and Wielenga, G.: Clinical aspects of urinary cytology. Acta Cytol., 16: 349, 1972. 4. Kern, W. H.: The cytology of transitional cell carcinoma of the urinary bladder. Acta Cytol., 19: 420, 1975. 5. Lewis, R. W., Jackson, A. C., Jr., Murphy, W. M., LeBlanc, A. and Meehan, W. L.: Cytology in the diagnosis and followup of transitional cell carcinoma .of the urothelium: a review with a case series. J. Urol., 116: 43, 1976 . 6, Prall, R.H., Wernett, C. and Mims, M. M.: Diagnostic cytology in urinary tract malignancy. Cancer, 29: 1084, l!J72. 7. Melicow, M. M.: Histological study of vesical urothelium inter·· vening between gross neoplasms in total cystectomy. J. Urol., 68: 261, 1952. 8. Schade, R 0. K. and Swinney, J.: The association of u.rothelial. atypism with neoplasia: its importance in treatment and prognosis. J. Urol., H}9: 619, 1973. 9. Althausen, A. F., Prout, G. R., Jr. and Daly, J. J.: Non-invasive papillary carcinoma of the bladder associated with carcinoma in situ. J. Urol., 116: 575, 1976. 10. Farrow, G. M., Utz, D. C. and Rife, C. C.: Morphological and clinical observations of patients with bladder cancer treated. with total cystectomy. Cancer Res., 2495, 1976. 11. Koss, L. G., Tiamson, E. M. and Robbins, 1\1!. A.: cancerous and precancerous bladder changes. A urotheliurn in ten surgically removed bladders. 227: 281, 1974. 12. Sarnacki, C. T., McCormack, L. McLaughlin, T. C. and Belovich, M.: Urinary the clinical diagnosis of urinary tract malignancy: a pathologic study of 1,400 patients. J. Urol., 106: 761, 1971. 13. Wiggishoff, C. C. and McDonald, J. H.: Urinary exfoliative cytology in tumors of the kidney and ureter. J. Ural., 170, 1969. 14. Allegra, S. R., Fanning, J. P., Streker, J. F. and Corvese, N. M.: Cytologic diagnosis of occult and "in-situ" carcinoma of the urinary system. Acta Cytol., HJ: 340, 1966. 15. Reece, R. W. and Koontz, W. W. · Jr.: Leukoplakia of the urinary tract: a review. J. Urol., 165, 1975. 16. Widran, J., Sanchez, R. and Gruhn, J.: Squamous uuecc1.i.n,"Ma of the bladder: a study of 450 patients. J. Urol., 112: 479,
THE ,.JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co.
URIN CYTOLOGY: PATHOLOGIST'S PRECLINICAL CANCER? ·wILLIAM M. MURPHY From the Department of Pathology, Unioersity of Tennessee Center for the Health Sciences, Memphis, Tennessee
ABSTRACT
The reluctance to
as a diagnostic in urologic cancer has been of falsely results. The recent of the identification of urothelial the
LU,~.CLH.,v
Hl
carcinoma in situ and bladder was available for found
Case 2. A black woman onset of gross, painless hematuria 4 tion. An IVP revealed a filling defect Initially, the defect was confirmed on rP1rrn,arcirlP and blood was emanating from the left ureter at Washings from the left renal suspicious of low grade ously obtained urine Subsequently, hematuria studies returned to normal. The matic with negative x-rays and has not returned to the clinic. Case 3. A black man with with gross, painless contained cells bladder On review, the
""ot,,c:f'nn.v
Patients with positiue or suspicious urinary cytology Histologic Diagnoses MATERIAL AND METHODS
Transitional cell Ca lViixsd (transitional-squamous) cell Ca Primary Metastatic Carcinoma in situ Moderate/severe dysplasia
records confirmed carcinoma (see with bladder cancer for whom urihad been requested. Six other had to severe urothelial dysplasia. The sis had not been confirmed at the termination of 10 who are discussed in detail.
No. Pb. 2
6 5
10 2 6
agam considered suspicious (part c of figure). underwent transurethral resection of the patient was last seen 3 months hematuria was noted. Case 4. A black man was referred to our from a nearby custodial care hospital. The vvas unreliable but on examination the patient had gross hematuria a greatly distended bladder. tumor cells were found in 1 of 3 urine specimens d of Bladder biopsies revealed mild urothelial rhagic or denuded. At farcts were found. A diagnosis. The patient was rehospitalized 2 months later for upper gastrointestinal bleeding of unknown source, No quent evaluation has been done. Case 5. A 50-year-old black woman and flank pain. Roentgenograms revealed a
CASE REPORTS
--,··-,~m
Accepted for publication February 25, 1977. 8ll
812
MURPHY
Cells initially considered positive or suspicious for malignancy. On review original diagnoses were confirmed in all but were reinterpreted as mild atypic and reactive urothelium, respectively. Reduced from x 400.
calculus and a questionable filling defect at the left ureterovesical junction. Cystoscopy was done as well as left ureteral catheterization but no stone was discovered. Before the cystoscopy 2 urine specimens and 1 bladder washing were obtained, all of which were negative for malignancy. A urine specimen collected after ureteral instrumentation had papillary aggregates suspicious of neoplasm. No bladder biopsy was done. On cytologic review the suspicious cells were reinterpreted as mild urothelial atypia (part e of figure). The patient is currently being followed in the clinic. Case 6. A 24-year-old white woman was 26 weeks pregnant when hospitalized with gross hematuria and left flank pain. Cystoscopy and retrograde pyelography revealed a tortuous and dilated left ureter. After ureteral instrumentation 2 urine specimens were submitted for cytologic studies, 1 of which was considered positive. On review, it was apparent that the specimens contained reactive rather than neoplastic papillary aggregates (part f of figure). Case 7. A 46-year-old black woman had been followed at regular intervals for 5 years before hospitalization. At the initial evaluation the patient had a squamous papilloma of the bladder and, thereafter, had had numerous bladder biopsies and fulgurations for squamous metaplasia. Recently, 1
e
and f, which
bladder washing contained cells suspicious of a low grade neoplasm. Two previous specimens and 2 subsequent samples have been negative. The original diagnosis was confirmed on cytologic review (part g of figure). The patient continues to have biopsy-proved squamous metaplasia. Case 8. A 72-year-old black man had had multiple episodes of gross, painless hematuria for 3 years before hospitalization. Two bladder biopsies had revealed denuded urothelium and chronic inflammation of the lamina propria. Multiple small diverticula had been identified in a cystogram. Of 5 urine specimens 1 contained malignant tumor cells (part h of figure). At cystoscopy a biopsy of a friable urothelial lesion yielded tissue with acute and organizing inflammation but denuded epithelium. Urine specimens 3 months later were negative for malignancy. A deep bladder biopsy at that time revealed interstitial inflammation consistent with eosinophilic cystitis. On review the original cytology specimen again was interpreted as positive. The patient is currently being followed by his physician in another state. Case 9. An 87-year-old black man had had biopsy-proved, incompletely resected adenocarcinoma of the prostate gland for 9 years at the time of hospitalization. Cytologic evaluation of a single urine specimen revealed cells suspicious of malig-
FALSELY POSITIVE URINARY CYTOLOGY
died before other studies for necropsy was denied. Case 10. An extensive search failed to uncover this records, uu.o,H.vu
DISCUSSION
studied 10 had not had histologic confirmation or susp1c1ous report. A review of clinical ..,a,,uvn,"''" material was possible in 9 cases. The original was confirmed in 7 and all of these abnormalities. remaining patients were and reactive cwc:uui,,, respectively. Both µo.cn,rn,o had had ureteral instrumentation before the "'1-''"·'rn,cu was collected. Reactive and even normal urothelial from the upper collecting are difficult to evalularge cells that tend to ate. :2 , 13 These areas are lined groups. may have mimic a low grade neoplasm of data (not provided in these cases) specimen misinterpretations of this kind can be avoided. Of the 7 cases with unconfirmed or suspicious and available records 2 had transient of the caliceal systems. In 1 blood was emanatthe corresponding ureteral orifice at cystoscopy. The abnormal cells occurred in 0pv~cm,,~
!JU!-'ULV>HU
The data also reflect the limitations of urinary ""toloau Cells from the upper collecting system may resemble low grade bladder cancer and, until cytologic criteria can be better defined, specimens from the ureters and/or renal should be noted. Any disease or procedure that such cells to appear in the urine should be rP,rrnrm,n positive or suspicious specimen, unsupported cli.nicaI findings, should not occasion extensive diagnostic and/or therapeutic procedures but neither should it be ignored. Positive or suspicious urinary cytology in the presence of bladder outlet obstruction and/or persistent, albeit apparently uroth·· elial abnormalities, such as squamous metaplasia, or extensive urothelial denudation, requires careful surveiJ. lance. REFERENCES
l.. Foot, N. C., Papanicolaou, G. N., Holmquist, N. D. and J. F.: Exfoliative cytology of urinary sediments. A 2,829 cases. Cancer, 11: 127, 1958. 2. Esposti, P. L., Moberger, G. and Zajicek, J.: The diagnosis of transitional cell tumors of the and its histologic basis. A study of 567 cases of disorder including 170 untreated and 182 irradiated tumors. Acta Cytol., 14: 145, 1970. 3. de Voogt, H. J. and Wielenga, G.: Clinical aspects of urinary cytology. Acta Cytol., 16: 349, 1972. 4. Kern, W. H.: The cytology of transitional cell carcinoma of the urinary bladder. Acta Cytol., 19: 420, 1975. 5. Lewis, R. W., Jackson, A. C., Jr., Murphy, W. M., LeBlanc, A. and Meehan, W. L.: Cytology in the diagnosis and followup of transitional cell carcinoma .of the urothelium: a review with a case series. J. Urol., 116: 43, 1976 . 6, Prall, R.H., Wernett, C. and Mims, M. M.: Diagnostic cytology in urinary tract malignancy. Cancer, 29: 1084, l!J72. 7. Melicow, M. M.: Histological study of vesical urothelium inter·· vening between gross neoplasms in total cystectomy. J. Urol., 68: 261, 1952. 8. Schade, R 0. K. and Swinney, J.: The association of u.rothelial. atypism with neoplasia: its importance in treatment and prognosis. J. Urol., H}9: 619, 1973. 9. Althausen, A. F., Prout, G. R., Jr. and Daly, J. J.: Non-invasive papillary carcinoma of the bladder associated with carcinoma in situ. J. Urol., 116: 575, 1976. 10. Farrow, G. M., Utz, D. C. and Rife, C. C.: Morphological and clinical observations of patients with bladder cancer treated. with total cystectomy. Cancer Res., 2495, 1976. 11. Koss, L. G., Tiamson, E. M. and Robbins, 1\1!. A.: cancerous and precancerous bladder changes. A urotheliurn in ten surgically removed bladders. 227: 281, 1974. 12. Sarnacki, C. T., McCormack, L. McLaughlin, T. C. and Belovich, M.: Urinary the clinical diagnosis of urinary tract malignancy: a pathologic study of 1,400 patients. J. Urol., 106: 761, 1971. 13. Wiggishoff, C. C. and McDonald, J. H.: Urinary exfoliative cytology in tumors of the kidney and ureter. J. Ural., 170, 1969. 14. Allegra, S. R., Fanning, J. P., Streker, J. F. and Corvese, N. M.: Cytologic diagnosis of occult and "in-situ" carcinoma of the urinary system. Acta Cytol., HJ: 340, 1966. 15. Reece, R. W. and Koontz, W. W. · Jr.: Leukoplakia of the urinary tract: a review. J. Urol., 165, 1975. 16. Widran, J., Sanchez, R. and Gruhn, J.: Squamous uuecc1.i.n,"Ma of the bladder: a study of 450 patients. J. Urol., 112: 479,
